To observe the therapeutic effect of Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis on serum osteopontin (OPN) and quality of life (QOL) in patients with primary Sjogren's syndrome (pSS) and to study the correlation between OPN level and the disease. Sixty-eight pSS patients were randomly assigned to two groups: the treatment group (35 cases) treated by Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis combined with hydroxychloroquine sulfate tablet (HCQ) and the control group (33 cases) treated by HCQ only. Both were treated for 3 months. Before and after treatment, immunoglobulin G (IgG) level, erythrocyte sedimentation rate (ESR), and OPN level were measured. The QOL in patients was evaluated using the Short Form-36 Health Survey (SF-36) before and after treatment. Thirty healthy females were taken as the normal control. Before treatment, levels of IgG, ESR, and OPN in patients were higher than those in the normal control. After 3 months of treatment, those in both treatment groups decreased but were lower in the treatment group than those in the control group (P<0.05). The scores of 8 dimensions of SF-36 were lower in the pSS patients than those in the normal control (P<0.05) and higher in the treatment group than in the control group after treatment (P<0.05). Furthermore, there was a positive correlation between the levels of OPN and the levels of IgG and ESR, and a negative correlation between OPN levels and the overall score of SF-36 (P<0.05). Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis could alleviate pSS disease and improve the QOL. In addition, the OPN level might be used as an evaluating index for pSS disease.